Vaccinia Virus Expressing Interferon Regulatory Factor 3 Induces Higher Protective Immune Responses against Lethal Poxvirus Challenge in Atopic Organism

Vaccinia Virus Expressing Interferon Regulatory Factor 3 Induces Higher Protective Immune Responses against Lethal Poxvirus Challenge in Atopic Organism

Vaccinia virus (VACV) is an enveloped DNA virus from the Orthopoxvirus family, various strains of which were used in the successful eradication campaign against smallpox. Both original and newer VACV-based replicating vaccines reveal a risk of serious complications in atopic individuals. VACV encode...

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Bibliographic Details
Published in:Viruses Vol. 13; no. 10; p. 1986
Main Authors: Pilna, Hana, Hajkova, Vera, Knitlova, Jarmila, Liskova, Jana, Elsterova, Jana, Melkova, Zora
Format: Journal Article
Language:English
Published: Switzerland MDPI AG 03-10-2021
MDPI
Subjects:
Acupuncture
Animals
Apoptosis
atopic dermatitis
Atopy
Body temperature
Dermatitis
DNA viruses
Eczema
eczema vaccinatum
Experiments
Gene Expression - genetics
Gene Expression Regulation, Viral - genetics
Immune response
Immunity - immunology
immunization
Infections
Interferon
Interferon regulatory factor
Interferon regulatory factor 3
Interferon Regulatory Factor-3 - genetics
Interferon Regulatory Factor-3 - immunology
Interferon Type I - metabolism
Interleukin-1beta - immunology
IRF-3
Laboratory animals
Lethal dose
Male
Medical research
Mice
Mice, Inbred BALB C
Phosphorylation
Poxviridae - pathogenicity
Poxviridae Infections - immunology
Poxviridae Infections - prevention & control
Skin
Skin - immunology
Smallpox
Vaccines
Vaccinia - virology
vaccinia virus
Vaccinia virus - genetics
Viral infections
Viral Vaccines - immunology
Virus Replication - immunology
Viruses
United States > US
Czech Republic
interferon beta
eczema vaccinatum
interleukin-1 beta
immunization
IRF-3
atopic dermatitis
cytokines
smallpox
vaccinia virus
Nc/Nga mice
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Summary:Vaccinia virus (VACV) is an enveloped DNA virus from the Orthopoxvirus family, various strains of which were used in the successful eradication campaign against smallpox. Both original and newer VACV-based replicating vaccines reveal a risk of serious complications in atopic individuals. VACV encodes various factors interfering with host immune responses at multiple levels. In atopic skin, the production of type I interferon is compromised, while VACV specifically inhibits the phosphorylation of the Interferon Regulatory Factor 3 (IRF-3) and expression of interferons. To overcome this block, we generated a recombinant VACV-expressing murine IRF-3 (WR-IRF3) and characterized its effects on virus growth, cytokine expression and apoptosis in tissue cultures and in spontaneously atopic Nc/Nga and control Balb/c mice. Further, we explored the induction of protective immune responses against a lethal dose of wild-type WR, the surrogate of smallpox. We demonstrate that the overexpression of IRF-3 by WR-IRF3 increases the expression of type I interferon, modulates the expression of several cytokines and induces superior protective immune responses against a lethal poxvirus challenge in both Nc/Nga and Balb/c mice. Additionally, the results may be informative for design of other virus-based vaccines or for therapy of different viral infections.
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Current affiliation: Department of Biomaterials and Tissue Engineering, Institute of Physiology, Czech Academy of Sciences, Videnska 1083, 142 20 Prague 4, Czech Republic.
Current affiliation: Institute of Parasitology, Biology Centre, Czech Academy of Sciences, Branisovska 31, 370 05 Ceske Budejovice, Czech Republic and Veterinary Research Institute, Hudcova 296/70, 621 00 Brno, Czech Republic.
The authors contributed equally to this work.
ISSN:1999-4915
1999-4915
DOI:10.3390/v13101986